Section: Scientific Foundations
Non ribosomal peptides synthesis
This theme started in 2003 by informal discussions between members of the ProbioGEM laboratory (biological processes, enzymatic and microbial engineering) from Université Lille 1 and members of our team. Non ribosomal peptides (NRPs) are small molecules (2 to 50 residues) that have a branching or cyclic structure and that can incorporate many non-standard amino acids. We realized that few bioinformatics tools dedicated to (NRPs) exist and that filling this lack should be an exciting challenge. The work really started with the coming of Ségolène Caboche in spring 2006 for her master thesis, followed by a PhD thesis, defended in September 2009. The objective of the thesis was to design a computational resource for working with nonribosomal peptides, called Norine .
Norine is available from summer 2006 at the website http://bioinfo.lifl.fr/norine/ . This first release has been announced in the Nucleic Acids Research 2008 database issue [1] . Today, the database contains 1116 nonribosomal peptides extracted from scientific literature with manually curated annotations such as biological activity, producing organisms or bibliographic references.
The database can be queried to search for peptides through their annotations as well as through their monomeric structure (structural pattern search or structure comparison). It also contains a section dedicated to the 506 different monomers incorporated into the peptides stored in Norine . We developed and implemented in Norine several efficient algorithms to compare NRP molecules represented as non-oriented labeled graphs. This led us to work on difficult computational problems in the field of graph isomorphism. We proposed an efficient algorithm that uses a variant of so-called compatibility graphs to search for all peptides containing a given structural pattern. The algorithm has been published in [14] , also containing some real-life biological examples of using this features for mining Norine for biologically useful information.
Currently, Norine is becoming the international reference resource for NRPs.
